Solution structure of a two-base DNA bulge complexed with an enediyne cleaving analog

Science

Volumn 272, Issue 5270, 1996, Pages 1943-1946

  Stassinopoulos, Adonis ^a,c   Ji, Jie ^b   Gao, Xiaolian ^b   Goldberg, Irving H ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b University of Houston   (United States)

^c Steritech Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CURVED DNA; DNA BASE; OLIGODEOXYNUCLEOTIDE; ZINOSTATIN;

ARTICLE; CATALYSIS; DNA CLEAVAGE; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL;

EID: 0030017851     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.272.5270.1943     Document Type: Article

References (49)

1. D. H. Turner, Curr. Opin. Struct. Biol. 2, 334 (1992); M. J. Lilley, Proc. Natl. Acad. Sci. U.S.A. 92, 7140 (1995), and references therein.
2. D. H. Turner, Curr. Opin. Struct. Biol. 2, 334 (1992); M. J. Lilley, Proc. Natl. Acad. Sci. U.S.A. 92, 7140 (1995), and references therein.
3. S. Feng and E. C. Holland, Nature 334, 165 (1988); C. Dingwall et al., EMBO J. 9, 4145 (1990); M. J. Gait and J. Karn, Trends Biochem. Sci. 18, 255 (1993).
4. S. Feng and E. C. Holland, Nature 334, 165 (1988); C. Dingwall et al., EMBO J. 9, 4145 (1990); M. J. Gait and J. Karn, Trends Biochem. Sci. 18, 255 (1993).
5. S. Feng and E. C. Holland, Nature 334, 165 (1988); C. Dingwall et al., EMBO J. 9, 4145 (1990); M. J. Gait and J. Karn, Trends Biochem. Sci. 18, 255 (1993).
6. S. Kleft and B. Kemper, EMBO J. 7, 1527 (1988).
7. T. A. Kunkel, Nature 365, 207 (1993).
8. L. S. Ripley, Proc. Natl. Acad. Sci. U.S.A. 79, 4128 (1982).
9. T. A. H. Hjaalt and E. G. H. Wagner, Nucleic Acids Res. 23, 580 (1995).
10. I. H. Goldberg and L. S. Kappen, in Enediyne Antibiotics as Antitumor Agents, D. B. Borders and T. W. Doyle, Eds. (Dekker, New York, 1994), pp. 327-362, and references therein; C. Nicolaou et al., Science 256, 1172 (1992).
11. I. H. Goldberg and L. S. Kappen, in Enediyne Antibiotics as Antitumor Agents, D. B. Borders and T. W. Doyle, Eds. (Dekker, New York, 1994), pp. 327-362, and references therein; C. Nicolaou et al., Science 256, 1172 (1992).
12. L. S. Kappen and I. H. Goldberg, Science 261, 1319 (1993); Biochemistry 32, 13138 (1993).
13. L. S. Kappen and I. H. Goldberg, Science 261, 1319 (1993); Biochemistry 32, 13138 (1993).
14. _, Biochemistry 34, 5997 (1995).
15. A. Stassinopoulos and I. H. Goldberg, ibid., p. 15359.
16. O. D. Hensens et al., Proc. Natl. Acad. Sci. U.S.A. 91, 4534 (1994); O. D. Hensens et al., J. Am. Chem. Soc. 115, 11030 (1993).
17. O. D. Hensens et al., Proc. Natl. Acad. Sci. U.S.A. 91, 4534 (1994); O. D. Hensens et al., J. Am. Chem. Soc. 115, 11030 (1993).
18. C. F. Yang, A. Stassinopoulos, I. H. Goldberg, Biochemistry 34, 2267 (1995).
19. NCSi-gb was prepared on a milligram scale from 1 by an improvement of the previously reported method (11). The synthesis of the oligonucleotide was as reported previously (12).
20. M. Durand et al., Nucleic Acids Res. 18, 6353 (1990).
21. X. Gao, A. Stassinopoulos, J. S. Rice, I. H. Goldberg, Biochemistry 34, 40 (1995).
22. K. Wüthrich, NMR of Proteins and Nucleic Acids (Wiley, New York, 1986).
23. 2O) aromatic base-H1′, H2′/H2″ sequential NOEs are interrupted at the A5-T6 (residues across from the bulge site) and T13-T14 steps and are extremely weak at the A11-A12 and A12-T13 steps.
24. G. J. Quigley et al., Proc. Natl. Acad. Sci. U.S.A. 77, 7204 (1980); X. Gao and D. J. Patel, Q. Rev. Biophys. 22, 93 (1989); M. Hansen, S. Yun, L. Hurley, Chem. Biol. 2, 229 (1995).
25. G. J. Quigley et al., Proc. Natl. Acad. Sci. U.S.A. 77, 7204 (1980); X. Gao and D. J. Patel, Q. Rev. Biophys. 22, 93 (1989); M. Hansen, S. Yun, L. Hurley, Chem. Biol. 2, 229 (1995).
26. G. J. Quigley et al., Proc. Natl. Acad. Sci. U.S.A. 77, 7204 (1980); X. Gao and D. J. Patel, Q. Rev. Biophys. 22, 93 (1989); M. Hansen, S. Yun, L. Hurley, Chem. Biol. 2, 229 (1995).
27. G. M. Crippen, Distance Geometry and Conformational Calculations (Wiley, New York, 1981); J. Kuszewski, M. Nilges, A. T. Brünger, J. Biomol. NMR 2, 33 (1992).
28. G. M. Crippen, Distance Geometry and Conformational Calculations (Wiley, New York, 1981); J. Kuszewski, M. Nilges, A. T. Brünger, J. Biomol. NMR 2, 33 (1992).
29. A. T. Brünger, G. M Clore, A. M. Gronenborn, M. Karplus, Proc. Natl. Acad. Sci. U.S.A. 83, 3801 (1986); M. Nilges, G. M. Clore, A. M. Gronenborn, FEBS Lett. 239, 129 (1988).
30. A. T. Brünger, G. M Clore, A. M. Gronenborn, M. Karplus, Proc. Natl. Acad. Sci. U.S.A. 83, 3801 (1986); M. Nilges, G. M. Clore, A. M. Gronenborn, FEBS Lett. 239, 129 (1988).
31. 4 Å; RMSD (bond angles), 1.839°.
32. M. Nilges, J. Habazettl, A. T. Brünger, T. A. Holak, J. Mol. Biol. 219, 499 (1991); T. James, Curr. Opin. Struct. Biol. 4, 275 (1994).
33. M. Nilges, J. Habazettl, A. T. Brünger, T. A. Holak, J. Mol. Biol. 219, 499 (1991); T. James, Curr. Opin. Struct. Biol. 4, 275 (1994).
34. Free DNA shows very weak sequential NOEs for the A12 and T13 bulged residues, as well as broadening of the resonances for their protons. These observations are consistent with a fluxional A12 and T13 bulged region with aromatic bases rotating in and out of the helix, distinctly different from a stable intrahelical A2 bulge, which has been shown to give well-defined NOEcross peaks [M. A. Rosen, D. Live, D. J. Patel, Biochemistry 31, 4004 (1992)].
35. The structure of the DNA in the complex is heterogeneous. Its positive inclination and displacement from the helical axis are closer to A- than B-DNA values. Although the δ angles are mostly B-like, the sugar pucker reflected by the phase angles is consistent with a range of sugar conformations [W. Saenger, Principles of Nucleic Acid Structure (Springer-Verlag, New York, 1984)].
36. S. A. Woodson and D. M. Crothers, Biochemistry 27, 3130 (1988); A. Bhattacharyya and D. M. J. Lilley, Nucleic Acids Res. 17, 6821 (1989); J. A. Rice and D. M. Crothers, Biochemistry 28, 4512 (1989).
37. S. A. Woodson and D. M. Crothers, Biochemistry 27, 3130 (1988); A. Bhattacharyya and D. M. J. Lilley, Nucleic Acids Res. 17, 6821 (1989); J. A. Rice and D. M. Crothers, Biochemistry 28, 4512 (1989).
38. S. A. Woodson and D. M. Crothers, Biochemistry 27, 3130 (1988); A. Bhattacharyya and D. M. J. Lilley, Nucleic Acids Res. 17, 6821 (1989); J. A. Rice and D. M. Crothers, Biochemistry 28, 4512 (1989).
39. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
40. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
41. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
42. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
43. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
44. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
45. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
46. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
47. For other efforts to find structure-specific nucleic acid interactive drugs see the following: W. D.Wilson et al., New J. Chem. 18, 419 (1994); and A. Slama-Schwok et al., J. Am. Chem. Soc. 117, 6822 (1995). Our structure contrasts with the one expected with simple intercalators that bind nonspecifically and nonexclusively at sites of single-base bulges [J. W. Nelson and I. Tinoco Jr., Biochemistry 24, 6416 (1985); S. A. White and D. E. Draper, Nucleic Acids Res. 15, 4049 (1987); D. Williams and I. H. Goldberg, Biochemistry 27, 3004 (1988)]. Similarly, polyaromatic chemical carcinogens covalently adducted to a DNA base can intercalate at duplex and bulge sites [L. M. Eckel and T. R. Krugh, Biochemisty 33, 13611 (1994); B. Mao et al., ibid. 34, 6226 (1995); B. Mao et al., ibid., p. 16641]. A solution structure of the complex formed between the intercalating antibiotic nogalamycin and a single-base bulge near the end of an oligonucleotide has recently been reported in which the drug acts as a duplex rather than a bulge binder because it obliterates the bulge by forcing base slippage [J. Caceres-Cortes and A. H.-J. Wang, Biochemistry 35, 616 (1996)].
48. A conformation change that brings the C2 and C8″ closer, induced by movement of the DNA in the complex, can be neither excluded nor proven with our data (8, 11). No significant amounts of 4 are produced in the absence of bulged DNA substrate.
49. This work was supported by U.S. Public Health Service grants CA 44257 and GM 53793 and from NIH to I.H.G., and an American Cancer Society grant JFRA-493 to X.G. The use of the Keck NMR and Computation Center at the University of Houston is acknowledged.